Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary for 3.4.11.2 extracted from

  • Xu, W.; Li, Q.
    Progress in the development of aminopeptidase N (APN/CD13) inhibitors (2005), Curr. Med. Chem., 5, 281-301.
    View publication on PubMed
Search for more literature for 3.4.11.2

Application

Application Comment Organism
drug development aminopeptidase N is a target for development of specific inhibitors Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(1S)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethanaminium acetate IC50: 70 nM Homo sapiens
(1S)-2-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethanaminium acetate IC50: 50 nM Homo sapiens
(1S)-3-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-aminium acetate IC50: 74 nM Homo sapiens
(4R)-4-(hexanoylamino)-N-hydroxy-1-[(3,4,5-trimethoxyphenyl)carbonyl]-L-prolinamide IC50: 7.7 nM Homo sapiens
(4R)-4-([(2E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino)-N-hydroxy-1-[(3,4,5-trimethoxyphenyl)carbonyl]-L-prolinamide IC50: 2.1 nM Homo sapiens
2-amino-2-phenylethanethiol IC50: 25 nM Homo sapiens
2-amino-3-(benzyloxy)propane-1-thiol IC50: 56 nM Homo sapiens
2-amino-3-(methylsulfanyl)propane-1-thiol IC50: 20 nM Homo sapiens
2-amino-3-(methylsulfinyl)propane-1-thiol IC50: 21 nM Homo sapiens
2-amino-3-(tert-butylsulfanyl)propane-1-thiol IC50: 40 nM Homo sapiens
2-amino-3-cyclohexylpropane-1-thiol IC50: 45 nM Homo sapiens
2-amino-3-phenylpropane-1-thiol IC50: 30 nM Homo sapiens
2-amino-4-(methylsulfanyl)butane-1-thiol IC50: 11 nM Homo sapiens
2-amino-4-(methylsulfinyl)butane-1-thiol IC50: 20 nM Homo sapiens
2-amino-4-methylpentane-1-thiol IC50: 22 nM Homo sapiens
3-amino-2-tetralones
-
 Homo sapiens
4-(2-amino-3-sulfanylpropyl)phenol IC50: 45 nM Homo sapiens
actinonin natural competitive inhibitor, IC50: 0.0002 mM Homo sapiens
amastatin natural competitive inhibitor from Streptomyces sp. Homo sapiens
anti-CD13 monoclonl antibody WM15 inhibits enzyme activity, but not chemotactic activity Homo sapiens
benzo[c]phenanthridine derivatives natural inhibitors Homo sapiens
bestatin narural competitive inhibitor, inhibits enzyme activity, but not chemotactic activity, IC50: 0.007-0.0169 mM Homo sapiens
beta-amino-alpha-hydroxyphenylbutanoic acid i.e. AHPA, or AHPA-VAl, natural inhibitor isolated from Streptomyces neyagawaensis strain SL-387, IC50: 0.0012-0.0056 mM Homo sapiens
betulinic acid natural inhibitor isolated from birch tree, IC50: 0.0073 mM, a selectively apoptosis-inducing agent, overview Homo sapiens
curcumin natural inhibitor isolated from Curcuma longa, non-toxic, inhibits also tumor cell invasion and carcinogenesis in several organs, overview Homo sapiens
ethyl D-cysteinate strong, competitive inhibition, IC50: 350 nM Homo sapiens
L-iso-glutamine inhibitors diverse derivatives, IC50 of 0.016-0.053 mM Homo sapiens
lapstatin natural competitive inhibitor from Streptomyces sp., IC50: 0.0005 mM Homo sapiens
leuhistin natural inhibitor isolated from Bacilus laterosporus strain BMI156-14F1, strong, competitive inhibition Homo sapiens
methyl (4R)-4-([(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino)-1-[(3,4,5-trimethoxyphenyl)carbonyl]-L-prolinate IC50: 0.9 nM Homo sapiens
additional information inhibitor binding site and mechanism, the enzyme is also inhibited by hydroxamate, carboxylate, sulfhydryl, and sulfodiimide derivatives of phosphoric acid, by beta-amino-thiol reagents, and alpha-aminophosphonates, overview Homo sapiens
N-[(2S)-2-(([(1R)-1-amino-2-phenylethyl](hydroxy)phosphoryl)methyl)-4-methylpentanoyl]-L-phenylalanine IC50: 2.3 nM Homo sapiens
N-[(2S)-3-([(1R)-1-amino-2-phenylethyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]-L-alanine IC50: 5.3 nM Homo sapiens
N-[(2S)-3-([(1R)-1-amino-2-phenylethyl](hydroxy)phosphoryl)-2-benzylpropanoyl]phenylalanine IC50: 1.5 nM Homo sapiens
N-[(2S)-3-([(1R)-1-aminoethyl](hydroxy)phosphoryl)-2-(4-bromobenzyl)propanoyl]-L-alanine IC50: 1.9 nM Homo sapiens
N-[(2S)-3-([(1R)-1-aminoethyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]alanine IC50: 2.9 nM Homo sapiens
N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]-L-alanine IC50: 4.8 nM Homo sapiens
N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]-L-serine IC50: 4.9 nM Homo sapiens
N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]-L-threonine IC50: 10.2 nM Homo sapiens
N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]glycine IC50: 32.8 nM Homo sapiens
N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-benzylpropanoyl]-L-phenylalanine IC50: 4.2 nM Homo sapiens
phebestin natural competitive inhibitor from Streptomyces sp. Homo sapiens
probestin natural competitive inhibitor from Streptomyces sp., IC50: 0.00005 mM Homo sapiens
psammaplin A natural inhibitor isolated from a marine sponge, non-competitive, highly cytotoxic, IC50: 0.007-0.018 mM, overview Homo sapiens
puromycin natural inhibitor Homo sapiens
[3-nitro-2-(2-nitrophenyl)-4-oxo-4H-chromen-8-yl]acetic acid IC50: 0.025 mM Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
cell surface ectoenzyme Homo sapiens 9986
-
plasma membrane type II membrane-bound ectoenzyme Homo sapiens 5886
-

Metals/Ions

Metals/Ions Comment Organism Structure
Zn2+ zinc-metalloendopeptidase, contains the conserved zinc-binding motif HEXXH, i.e. HEALH-X18E, binds to the active site Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
bradykinin + H2O Homo sapiens
-
 ?
-
 ?
interleukin-8 + H2O Homo sapiens
-
 ?
-
 ?
Leu-enkephalin + H2O Homo sapiens
-
 Leu + enkephalin
-
 ?
additional information Homo sapiens the enzyme is involved in hydrolysis of neutral or basic amino acids from the N-terminus of bioactive peptides, or of amide or arylamide derivatives of amino acids, the enzyme promotes malignant angiogenesis/tumorigenesis, cell proliferation and tumor cell growth, and is involved in several diseases, e.g. inflammatory, overview, detailed catalytic machanism ?
-
 ?
Substance P + H2O Homo sapiens
-
 ?
-
 ?
thymopentin + H2O Homo sapiens
-
 ?
-
 ?
tuftsin + H2O Homo sapiens
-
 ?
-
 ?

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
glycoprotein
-
 Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
T-lymphocyte
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
bradykinin + H2O
-
 Homo sapiens ?
-
 ?
interleukin-8 + H2O
-
 Homo sapiens ?
-
 ?
Leu-enkephalin + H2O
-
 Homo sapiens Leu + enkephalin
-
 ?
additional information the enzyme is involved in hydrolysis of neutral or basic amino acids from the N-terminus of bioactive peptides, or of amide or arylamide derivatives of amino acids, the enzyme promotes malignant angiogenesis/tumorigenesis, cell proliferation and tumor cell growth, and is involved in several diseases, e.g. inflammatory, overview, detailed catalytic machanism Homo sapiens ?
-
 ?
Substance P + H2O
-
 Homo sapiens ?
-
 ?
thymopentin + H2O
-
 Homo sapiens ?
-
 ?
tuftsin + H2O
-
 Homo sapiens ?
-
 ?

Subunits

Subunits Comment Organism
dimer homodimer, domain structure comprising cytosolic domain, transmembrane alpha-helix domain, N-glycosylation domain, polyproline and O-glycosylation domain, active site domain containing HEALH-X18E motif, and dimerization domain containing charged amino acids, overview Homo sapiens

Synonyms

Synonyms Comment Organism
aminopeptidase N
-
 Homo sapiens
APN
-
 Homo sapiens
CD13
-
 Homo sapiens
More the enzyme belongs to the peptidase family M1 Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000019
-
 probestin
-
 Homo sapiens
0.00023
-
 leuhistin
-
 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.0000009
-
 IC50: 0.9 nM Homo sapiens methyl (4R)-4-([(2E)-3-(3,4-dihydroxyphenyl)prop-2-enoyl]amino)-1-[(3,4,5-trimethoxyphenyl)carbonyl]-L-prolinate
0.0000015
-
 IC50: 1.5 nM Homo sapiens N-[(2S)-3-([(1R)-1-amino-2-phenylethyl](hydroxy)phosphoryl)-2-benzylpropanoyl]phenylalanine
0.0000019
-
 IC50: 1.9 nM Homo sapiens N-[(2S)-3-([(1R)-1-aminoethyl](hydroxy)phosphoryl)-2-(4-bromobenzyl)propanoyl]-L-alanine
0.0000021
-
 IC50: 2.1 nM Homo sapiens (4R)-4-([(2E)-3-(3,4-dimethoxyphenyl)prop-2-enoyl]amino)-N-hydroxy-1-[(3,4,5-trimethoxyphenyl)carbonyl]-L-prolinamide
0.0000023
-
 IC50: 2.3 nM Homo sapiens N-[(2S)-2-(([(1R)-1-amino-2-phenylethyl](hydroxy)phosphoryl)methyl)-4-methylpentanoyl]-L-phenylalanine
0.0000029
-
 IC50: 2.9 nM Homo sapiens N-[(2S)-3-([(1R)-1-aminoethyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]alanine
0.0000042
-
 IC50: 4.2 nM Homo sapiens N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-benzylpropanoyl]-L-phenylalanine
0.0000048
-
 IC50: 4.8 nM Homo sapiens N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]-L-alanine
0.0000049
-
 IC50: 4.9 nM Homo sapiens N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]-L-serine
0.0000053
-
 IC50: 5.3 nM Homo sapiens N-[(2S)-3-([(1R)-1-amino-2-phenylethyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]-L-alanine
0.0000077
-
 IC50: 7.7 nM Homo sapiens (4R)-4-(hexanoylamino)-N-hydroxy-1-[(3,4,5-trimethoxyphenyl)carbonyl]-L-prolinamide
0.0000102
-
 IC50: 10.2 nM Homo sapiens N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]-L-threonine
0.000011
-
 IC50: 11 nM Homo sapiens 2-amino-4-(methylsulfanyl)butane-1-thiol
0.00002
-
 IC50: 20 nM Homo sapiens 2-amino-4-(methylsulfinyl)butane-1-thiol
0.00002
-
 IC50: 20 nM Homo sapiens 2-amino-3-(methylsulfanyl)propane-1-thiol
0.000021
-
 IC50: 21 nM Homo sapiens 2-amino-3-(methylsulfinyl)propane-1-thiol
0.000022
-
 IC50: 22 nM Homo sapiens 2-amino-4-methylpentane-1-thiol
0.000025
-
 IC50: 25 nM Homo sapiens 2-amino-2-phenylethanethiol
0.00003
-
 IC50: 30 nM Homo sapiens 2-amino-3-phenylpropane-1-thiol
0.0000328
-
 IC50: 32.8 nM Homo sapiens N-[(2S)-3-([(R)-amino(phenyl)methyl](hydroxy)phosphoryl)-2-(biphenyl-4-ylmethyl)propanoyl]glycine
0.00004
-
 IC50: 40 nM Homo sapiens 2-amino-3-(tert-butylsulfanyl)propane-1-thiol
0.000045
-
 IC50: 45 nM Homo sapiens 2-amino-3-cyclohexylpropane-1-thiol
0.000045
-
 IC50: 45 nM Homo sapiens 4-(2-amino-3-sulfanylpropyl)phenol
0.00005
-
 IC50: 50 nM Homo sapiens (1S)-2-phenyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethanaminium acetate
0.00005
-
 natural competitive inhibitor from Streptomyces sp., IC50: 0.00005 mM Homo sapiens probestin
0.000056
-
 IC50: 56 nM Homo sapiens 2-amino-3-(benzyloxy)propane-1-thiol
0.00007
-
 IC50: 70 nM Homo sapiens (1S)-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethanaminium acetate
0.000074
-
 IC50: 74 nM Homo sapiens (1S)-3-methyl-1-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butan-1-aminium acetate
0.0002
-
 natural competitive inhibitor, IC50: 0.0002 mM Homo sapiens actinonin
0.00035
-
 strong, competitive inhibition, IC50: 350 nM Homo sapiens ethyl D-cysteinate
0.0005
-
 natural competitive inhibitor from Streptomyces sp., IC50: 0.0005 mM Homo sapiens lapstatin
0.0012 0.0056 i.e. AHPA, or AHPA-VAl, natural inhibitor isolated from Streptomyces neyagawaensis strain SL-387, IC50: 0.0012-0.0056 mM Homo sapiens beta-amino-alpha-hydroxyphenylbutanoic acid
0.007 0.0169 narural competitive inhibitor, inhibits enzyme activity, but not chemotactic activity, IC50: 0.007-0.0169 mM Homo sapiens bestatin
0.007 0.018 natural inhibitor isolated from a marine sponge, non-competitive, highly cytotoxic, IC50: 0.007-0.018 mM, overview Homo sapiens psammaplin A
0.0073
-
 natural inhibitor isolated from birch tree, IC50: 0.0073 mM, a selectively apoptosis-inducing agent, overview Homo sapiens betulinic acid
0.016 0.053 diverse derivatives, IC50 of 0.016-0.053 mM Homo sapiens L-iso-glutamine inhibitors
0.025
-
 IC50: 0.025 mM Homo sapiens [3-nitro-2-(2-nitrophenyl)-4-oxo-4H-chromen-8-yl]acetic acid